Activation of thalamo-cortical circuits with posterior hypothalamic nucleus deep brain stimulation

Abstract

The posterior hypothalamic nucleus (PH) has extensive anatomical connections to motor, cognitive, visceral, and homeostatic areas of the brain and serves as a crucial subcortical modulator of behaviour. Previous studies have demonstrated that deep brain stimulation (DBS) of this area can lead to powerful activation of motor behaviour, overcoming two rodent models of parkinsonian akinesia by increasing neocortical excitability. However, it is unclear how the PH may mediate this increase in neocortical excitability. In the present study, we examined the role of the thalamus in the PH-DBS mediated increase in neocortical excitability. In urethane anaesthetized animals, we demonstrate that PH-DBS elicits increased spiking activity in the motor thalamus (VL) that receives direct afferents from the PH that precedes the increase in spiking activity in the corresponding motor cortex. In contrast, in the somatosensory thalamus (VPM) where PH afferents are sparse at best, PH-DBS did not elicit an increase in thalamic activity despite of a slight increase in the corresponding somatosensory cortical spiking. Current source density analyses suggest a thalamo-cortical mechanism for motor cortex activation whereas a cortico-cortical activation mechanism is involved in somatosensory cortical activation. Inactivation of the VL resulted in the abolition of motor cortex spiking despite of the persistence of desynchronized field potential activity. Collectively, these data suggest indirect orthodromic activation of PH output fibres to the thalamus mediates increased neocortical excitation, which may spread through cortico-cortical connections and lead to an increase in integrated, non-stereotypical motor behaviour.